Associations of prenatal heavy metals exposure with placental characteristics and birth weight in Hangzhou Birth Cohort: Multi-pollutant models based on elastic net regression

Abstract Background The human placenta is vulnerable to environmental pollutants, but the associations between exposure to multiple, correlated metals and placental characteristics have not been studied. Methods The current study population was derived from the Hangzhou Birth Cohort Study. Whole blood and urine samples were collected from mothers during 20–28 gestational week. The concentrations of 11 metals in blood and 11 metals in urine were evaluated by inductively coupled plasma mass spectrometry. The data on placental characteristics and birth weight were retrieved from medical records. The elastic net (ENET) model combined with unpenalized regression model was employed to estimate the relationship between levels of metals and placental characteristics (placental weight, chorionic disc area, chorionic disc eccentricity, placental thickness, placental-fetal birth weight ratio) and birth weight. Mediation analysis was performed to explore the mediated effect of placenta on the association of prenatal metals exposure with birth weight. Results Among 512 participants with urine metal levels, the ENET model retained Cadmium (Cd) and Selenium (Se) for placental weight. Further unpenalized regression model including Cd and Se simultaneously showed that one-unite increased natural-logarithm (ln)-transformed urine creatinine corrected (CC) Cd levels was associated with reductions in placental weight of −7.2 g (95% confidence interval (CI): −14.0, −0.4). Among 483 participants with blood metal levels, similarly, blood Cd levels were negatively associated with placental weight (β = −7.5, 95% CI: −17.0, 1.9). Furthermore, mediation analysis demonstrated that urine CC-Cd level was associated with a 21.3 g decrease (95% CI: −42.0, −2.5, p = 0.024) in birth weight through a reduction in placental weight, while blood Cd levels presented a negative association at borderline significance. Conclusion Our findings suggest a mediation effect of the placenta in the relationship between prenatal Cd exposure and lower birth weight. Additional studies with repeated assessment of exposure and more placental parameters are warranted to confirm this relationship.